Impact of prior axonal injury on subsequent injury during brain tissue stretching - A mesoscale computational approach.

Epidemiology studies of traumatic brain injury (TBI) show individuals with a prior history of TBI experience an increased risk of future TBI with a significantly more detrimental outcome. But the mechanisms through which prior head injuries may affect risks of injury during future head insults have not been identified. In this work, we show that prior brain tissue injury in the form of mechanically induced axonal injury and glial scar formation can facilitate future mechanically induced tissue injury. To achieve this, we use finite element computational models of brain tissue and a history-dependent pathophysiology-based mechanically-induced axonal injury threshold to determine the evolution of axonal injury and scar tissue formation and their effects on future brain tissue stretching. We find that due to the reduced stiffness of injured tissue and glial scars, the existence of prior injury can increase the risk of future injury in the vicinity of prior injury during future brain tissue stretching. The softer brain scar tissue is shown to increase the strain and strain rate in its vicinity by as much as 40% in its vicinity during dynamic stretching that reduces the global strain required to induce injury by 20% when deformed at 15 s-1 strain rate. The results of this work highlight the need to account for patient history when determining the risk of brain injury.

Effect of Force Field Resolution on Membrane Mechanical Response and Mechanoporation Damage under Deformation Simulations.

Damage induced by transient disruption and mechanoporation in an intact cell membrane is a vital nanoscale biomechanical mechanism that critically affects cell viability. To complement experimental studies of mechanical membrane damage and disruption, molecular dynamics (MD) simulations have been performed at different force field resolutions, each of which follows different parameterization strategies and thus may influence the properties and dynamics of membrane systems. Therefore, the current study performed tensile deformation MD simulations of bilayer membranes using all-atom (AA), united-atom (UA), and coarse-grained Martini (CG-M) models to investigate how the damage biomechanics differs across atomistic and coarse-grained (CG) simulations. The mechanical response and mechanoporation damage were qualitatively similar but quantitatively different in the three models, including some progressive changes based on the coarse-graining level. The membranes yielded and reached ultimate strength at similar strains; however, the coarser systems exhibited lower average yield stresses and failure strains. The average failure strain in the UA model was approximately 7% lower than the AA, and the CG-M was 20% lower than UA and 27% lower than AA. The CG systems also nucleated a higher number of pores and larger pores, which resulted in higher damage during the deformation process. Overall, the study provides insight on the impact of force field-a critical factor in modeling biomolecular systems and their interactions-in inspecting membrane mechanosensitive responses and serves as a reference for justifying the appropriate force field for future studies of more complex membranes and more diverse biomolecular assemblies.